Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice.

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

Anti-obesity effects of Celosia cristata flower extract in vitro and in vivo.

BACKGROUND: The overstoring of surplus calories in mature adipocytes causes obesity and abnormal metabolic activity. The anti-obesity effect of a Celosia cristata (CC) total flower extract was assessed in vitro, using 3T3-L1 pre-adipocytes and mouse adipose-derived stem cells (ADSCs), and in vivo, using high-fat diet (HFD)-treated C57BL/6 male mice. METHODS: CC extract was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs. After differentiation, lipid droplets were assessed by oil red O staining, adipogenesis and lipolytic factors were evaluated, and intracellular triglyceride and glycerol concentrations were analyzed. For in vivo experiments, histomorphological analysis, mRNA expression levels of adipogenic and lipolytic factors in adipose tissue, blood plasma analysis, metabolic profiles were investigated. RESULTS: CC treatment significantly prevented adipocyte differentiation and lipid droplet accumulation, reducing adipogenesis-related factors and increasing lipolysis-related factors. Consequently, the intracellular triacylglycerol content was diminished, whereas the glycerol concentration in the cell supernatant increased. Mice fed an HFD supplemented with the CC extract exhibited decreased HFD-induced weight gain with metabolic abnormalities such as intrahepatic lipid accumulation and adipocyte hypertrophy. Improved glucose utilization and insulin sensitivity were observed, accompanied by the amelioration of metabolic disturbances, including alterations in liver enzymes and lipid profiles, in CC-treated mice. Moreover, the CC extract helped restore the disrupted energy metabolism induced by the HFD, based on a metabolic animal monitoring system. CONCLUSION: This study suggests that CC total flower extract is a potential natural herbal supplement for the prevention and management of obesity.

Anti-Osteoarthritic Effects of Prunella Vulgaris and Gentiana Lutea In Vitro and In Vivo.

Osteoarthritis (OA) is the progressive destruction of articular cartilage with severe symptoms, including pain and stiffness. We investigated the anti-osteoarthritic effects of Prunella vulgaris (PV) and Gentiana lutea (GL) extract in primary cultured chondrocytes RAW 264.7 cells in vitro and destabilization of the medial meniscus (DMM)-induced OA mice in vivo. Primary chondrocytes were induced with IL-1ß, and RAW 264.7 cells were treated with LPS and co-incubated with either individual extracts of PV and GL or different ratios of PV and GL mixture. For the OA animal model, the medial meniscus (DMM) was destabilized in 9-week-old male C57BL/6 mice. Treatment of individual PV and GL and combination of PV and GL extracts inhibited the mRNA expression level of COX2 in chondrocytes and RAW 264.7 cells. The optimized inhibitory effect was attained with a PV and GL combination at an 8:2 ratio (PG) without cytotoxic effects. PG extracts prevented the expression of catabolic factors (COX2, Mmp3, Mmp9, and Mmp13) and inflammatory mediator levels (PGE2 and collagenase). In addition, PG decreased subchondral sclerosis and increased BMD in the subchondral region of DMM-induced OA mice with protection of articular cartilage destruction by inhibiting inflammatory processes. This study suggests that PG may be an alternative medicinal herb for treatment of OA.

Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice.

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

Anti-Menopausal Effects of Cornus officinalis and Ribes fasciculatum Extract In Vitro and In Vivo.

: Natural herbal medicines have been developed for the treatment and prevention of women's menopausal symptoms. In this study, we investigated the anti-menopausal effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) extracts in 3T3-L1 preadipocytes, MC3T3-E1 preosteoblasts, and COV434 granulosa cells in vitro and ovariectomized (OVX) ddY mice in vivo. Combination treatment of CO and RF extract at 7:3 ratio inhibited lipid accumulation via Plin1 and Adipoq downregulation in a cocktail of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin (DMI)-induced differentiated 3T3-L1 cells. In addition, CO + RF treatment significantly enhanced osteoblastic differentiation, with mineralized nodule formation occurring through the upregulation of osteoblast-inducing markers in osteoblastic MC3T3-E1 cells. Increased production of estradiol and mRNA expression of ERα (ESR1) were observed in androstenedione-induced COV434 granulosa cells treated with the CO + RF extract. In CO + RF-treated mice, fatty hepatocyte deposition and abdominal visceral fat tissues reduced with OVX-induced uterine atrophy. Furthermore, bone mineral density and bone mineral content were significantly enhanced by CO + RF in mouse models of ovariectomy-induced femoral bone loss. Taken together, our findings suggested that CO + RF promoted estrogenic activity and had anti-obesity and anti-osteoporotic effects in vitro and in vivo. Thus, a combination of CO and RF extracts may be a good therapeutic strategy for managing women's menopausal syndromes.

Anti-Osteoporotic Effects of the Herbal Mixture of Cornus officinalis and Achyranthes japonica In Vitro and In Vivo.

Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.